B. Introduction This project propose to study the pathogenesis of Theiler's murine encephalitis virus (TMEV) in mice as a function of age. TMEV is an enterovirus and a natural pathogen of mice closely related to important human pathogens. The virus is known to establish persistent infection in mice and age appears to be a critical determinant of disease patterns. The information to be gathered during this study will potentially be of great benefit to our understanding and management of human diseases caused by enteroviruses. We propose to study the relationship of RNA virus pathogenesis and aging a different, yet equally challenging task as that of the DNA viral work being proposed.